Zhencui Zhang , Shouyang Ren , Xinyi Fan , Huiying Chen , Jiaheng Chen , Xiaoqian Wang , Han Zong , Shengshuai Zhang , Tianyi Zhao , Yujie Sun , Ruixin Pang , Wengang Song , Wen Zhang , Ben Wang , Zhengtao Chen , Li Ge
{"title":"慢性心理应激介导神经胶质- ilc3回路加重肠道炎症和抑郁。","authors":"Zhencui Zhang , Shouyang Ren , Xinyi Fan , Huiying Chen , Jiaheng Chen , Xiaoqian Wang , Han Zong , Shengshuai Zhang , Tianyi Zhao , Yujie Sun , Ruixin Pang , Wengang Song , Wen Zhang , Ben Wang , Zhengtao Chen , Li Ge","doi":"10.1016/j.bbi.2025.106118","DOIUrl":null,"url":null,"abstract":"<div><div>Chronic psychological stress can exacerbate intestinal inflammation both in patients with inflammatory bowel disease (IBD) and animal models of experimental colitis, but the underlying mechanism remains poorly understood. Here, we identified a chronic stress-orchestrated intestinal glia-Group 3 innate lymphoid cell (ILC3) circuit that impairs innate interleukin (IL)–22-mediated immune protection. We found that stress promoted the release of excessive amounts of glucocorticoid (GC) by the adrenal cortex through activation of the hypothalamic–pituitary–adrenal axis. Subsequently, chronically elevated level of GC dysregulated the phenotype and function of enteric glial cells (EGCs) through binding to the glucocorticoid receptor on EGCs, thereby weakening glial-derived neurotrophic factor production. These lead to the deficiency of innate IL-22 and impairment of gut defense. Simultaneously, we demonstrated that exacerbation of intestinal inflammation further unleashes the progression of neuroinflammation and anxiety/depression-like behaviors. Our work sheds light on a novel mechanism by which chronic psychological stress exacerbates intestinal inflammation, expanding the understanding of ILC3 biology and ILC3-mediated mucosal immunity. We proposed an innate IL-22-based therapeutic strategy for IBD patients with psychological comorbidities, and suggested stress management as a valuable component of IBD care in the context of bidirectional brain-gut communication.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"130 ","pages":"Article 106118"},"PeriodicalIF":7.6000,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Chronic psychological stress-orchestrated glial-ILC3 circuit exacerbates intestinal inflammation and depression\",\"authors\":\"Zhencui Zhang , Shouyang Ren , Xinyi Fan , Huiying Chen , Jiaheng Chen , Xiaoqian Wang , Han Zong , Shengshuai Zhang , Tianyi Zhao , Yujie Sun , Ruixin Pang , Wengang Song , Wen Zhang , Ben Wang , Zhengtao Chen , Li Ge\",\"doi\":\"10.1016/j.bbi.2025.106118\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Chronic psychological stress can exacerbate intestinal inflammation both in patients with inflammatory bowel disease (IBD) and animal models of experimental colitis, but the underlying mechanism remains poorly understood. Here, we identified a chronic stress-orchestrated intestinal glia-Group 3 innate lymphoid cell (ILC3) circuit that impairs innate interleukin (IL)–22-mediated immune protection. We found that stress promoted the release of excessive amounts of glucocorticoid (GC) by the adrenal cortex through activation of the hypothalamic–pituitary–adrenal axis. Subsequently, chronically elevated level of GC dysregulated the phenotype and function of enteric glial cells (EGCs) through binding to the glucocorticoid receptor on EGCs, thereby weakening glial-derived neurotrophic factor production. These lead to the deficiency of innate IL-22 and impairment of gut defense. Simultaneously, we demonstrated that exacerbation of intestinal inflammation further unleashes the progression of neuroinflammation and anxiety/depression-like behaviors. Our work sheds light on a novel mechanism by which chronic psychological stress exacerbates intestinal inflammation, expanding the understanding of ILC3 biology and ILC3-mediated mucosal immunity. We proposed an innate IL-22-based therapeutic strategy for IBD patients with psychological comorbidities, and suggested stress management as a valuable component of IBD care in the context of bidirectional brain-gut communication.</div></div>\",\"PeriodicalId\":9199,\"journal\":{\"name\":\"Brain, Behavior, and Immunity\",\"volume\":\"130 \",\"pages\":\"Article 106118\"},\"PeriodicalIF\":7.6000,\"publicationDate\":\"2025-09-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Brain, Behavior, and Immunity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0889159125003605\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Brain, Behavior, and Immunity","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0889159125003605","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Chronic psychological stress-orchestrated glial-ILC3 circuit exacerbates intestinal inflammation and depression
Chronic psychological stress can exacerbate intestinal inflammation both in patients with inflammatory bowel disease (IBD) and animal models of experimental colitis, but the underlying mechanism remains poorly understood. Here, we identified a chronic stress-orchestrated intestinal glia-Group 3 innate lymphoid cell (ILC3) circuit that impairs innate interleukin (IL)–22-mediated immune protection. We found that stress promoted the release of excessive amounts of glucocorticoid (GC) by the adrenal cortex through activation of the hypothalamic–pituitary–adrenal axis. Subsequently, chronically elevated level of GC dysregulated the phenotype and function of enteric glial cells (EGCs) through binding to the glucocorticoid receptor on EGCs, thereby weakening glial-derived neurotrophic factor production. These lead to the deficiency of innate IL-22 and impairment of gut defense. Simultaneously, we demonstrated that exacerbation of intestinal inflammation further unleashes the progression of neuroinflammation and anxiety/depression-like behaviors. Our work sheds light on a novel mechanism by which chronic psychological stress exacerbates intestinal inflammation, expanding the understanding of ILC3 biology and ILC3-mediated mucosal immunity. We proposed an innate IL-22-based therapeutic strategy for IBD patients with psychological comorbidities, and suggested stress management as a valuable component of IBD care in the context of bidirectional brain-gut communication.
期刊介绍:
Established in 1987, Brain, Behavior, and Immunity proudly serves as the official journal of the Psychoneuroimmunology Research Society (PNIRS). This pioneering journal is dedicated to publishing peer-reviewed basic, experimental, and clinical studies that explore the intricate interactions among behavioral, neural, endocrine, and immune systems in both humans and animals.
As an international and interdisciplinary platform, Brain, Behavior, and Immunity focuses on original research spanning neuroscience, immunology, integrative physiology, behavioral biology, psychiatry, psychology, and clinical medicine. The journal is inclusive of research conducted at various levels, including molecular, cellular, social, and whole organism perspectives. With a commitment to efficiency, the journal facilitates online submission and review, ensuring timely publication of experimental results. Manuscripts typically undergo peer review and are returned to authors within 30 days of submission. It's worth noting that Brain, Behavior, and Immunity, published eight times a year, does not impose submission fees or page charges, fostering an open and accessible platform for scientific discourse.